MRI visualization of multiple sclerosis lesions

Magnetic resonance imaging represents voxels (volume elements) of the body placed in a magnet, by their magnetization determined under various acquisition conditions weighting the contrast of the image by the density of free water protons and their relaxation times T1 and T2. Thus, the sensitivity in depicting lesions is high but pathological specificity is poor. Efforts are made to increase the diagnosis powerfulness of M.R.I. in multiple sclerosis: a careful correlation with the clinical presentation and the use of better M.R.I. criteria increase the specificity of the conventional T2 sequences. New sequences such as fast spin echo (F.S.E.), turbo spin echo (T.S.E.) or derived from inversion recovery (F.L.A.I.R.: fluid attenuated inversion recovery) improve the detection of lesions. Under specific conditions M.R.I. can be used to monitor the evolution of M.S. Acute phase monitoring focuses on changes in disease activity, new, recurring, enlarging, gadolinium (Gd) enhancing lesions, and chronic phase monitoring appreciate the burden of the disease. However M.R.I. is always considered as a secondary outcome in the phase III trials because insufficient correlations with the clinical disability. In the neurological daily practice conventional M.R.I. is of poor interest in the follow up of individual M.S. patients considering the weakness of prognosis value and the problems in the measurement of the lesions load which is emphasized in the methodology of the clinical trials. Nevertheless, there is a continuing search for techniques which correlate better with clinical measures of the disease such as the quantification of "black holes" on T1 w images or the cerebral and spinal atrophy. New techniques allow to weight the signal by the movement (diffusion imaging), by the complexity of the molecular architecture (magnetization transfer imaging), by the chemical shift (chemical shift imaging) or by the local status of oxygenation (functional M.R.I.). The basic aspects of the pathological lesions in M.S., edema, membrane disruption, demyelination, gliosis, cellular infiltration and axonal loss can be studied more precisely by these new M.R. techniques which should better describe the actual clinical impact of the destructive process. In the last year the importance of axonal loss has simultaneously been confirmed by M. R. spectroscopy and pathological findings. However, magnetization transfer imaging, M.R. diffusion imaging and functional M.R.I. are intensively under investigation for a better analysis of these different factors conditioning the reversibility of the patient disability.     

Influenza vaccination in patients with multiple sclerosis

Vaccination was well tolerated by 93 patients with multiple sclerosis who received a total of 209 doses of influenza vaccine. In one patient, evidence of a new lesion developed after vaccination; the relapse rate was less than would be expected in the natural course of the illness. Toxic and allergic reactions appeared with 7% and 0.5% of the vaccinations, respectively--a rate no higher than that observed in the general population.     

Lipid peroxidation in patients with multiple sclerosis

Questions of lipid metabolism in patients with multiple sclerosis are considered in the light of biomembrane (myelin) pathology. The results of of the study of the lipids fatty acids spectrum in the blood plasma and the secondary product of their spontaneous and NADPhH-dependent peroxidation, malonic dialdehyde, are stated. The dependence of changes in saturation of fatty acids spectrum and dialdehyde concentrations on the stage and heaviness of the multiple sclerosis is shown. Certain dynamics of lipid metabolism indices as a result of treatment was found. The authors also give some recommendations as to the use of drugs at various stages of the disease.     

Correlating MR lesions and functional deficits in multiple sclerosis patients. Anatomical atlas registration

Although brain magnetic resonance (MR) imaging is increasingly being used as an objective outcome measure in treatment trials for multiple sclerosis (MS), findings correlating conventional MR imaging and disabilities in established MS have been inconsistent. In some studies, measures of MR lesion status, such as numbers of lesions or MS lesion load (volume), have shown limited correlations with clinical scores such as the Kurtzke Expanded disability scale (EDSS). Other studies have shown clear correlations between MR findings and measures of disability in MS. Further development of image processing techniques should help elucidate the relationships between MR findings and disease processes in MS.     

Axonal transection in the lesions of multiple sclerosis

We explored the relationship between mutans streptococcal infection and the development of salivary IgA antibody during initial colonization. Repetitive swabbing (n = 292) of the teeth of 33 children revealed that 45% became infected with mutans streptococci between 13 and 36 months of age. In contrast, mutans streptococci could not be detected in 18 children whose last sample was taken at 39-81 months of age (median age = 62 months). During the period of mutans streptococcal infectivity, immunoglobulin A (IgA) antibody to several mutans streptococcal antigens appeared in most children, whether or not infection had been demonstrated. Robust responses to mutans streptococcal components occurred during or shortly after, but not before the period of mutans streptococcal infectivity. No consistent differences were observed among the summarized patterns of response of infected and uninfected groups of children, although the IgA Western blot patterns of individual subjects were often quite distinct. For example, sets of siblings, who would be presumed to be challenged with similar maternal mutans streptococcal clonotypes, were shown to develop qualitatively different salivary IgA responses to mutans streptococcal components. These results support a discrete period for mutans streptococcal infection and may suggest that the level of maternal infection is a factor in the success of infection of the child during this period. The data also suggest that exposure to mutans streptococci is a sufficient condition for robust mucosal IgA responses to mutans streptococcal antigens during the period of infectivity and that these responses may be different, even among siblings.     

Bladder cancer in patients with multiple sclerosis treated with cyclophosphamide

PURPOSE: We define the risk of bladder cancer in multiple sclerosis related to the use of indwelling catheters and cyclophosphamide administered as an immunomodulating agent. MATERIALS AND METHODS: We retrospectively reviewed the records of 2,351 patients with multiple sclerosis referred to the National Center for Multiple Sclerosis. RESULTS: Of the 2,351 patients 2 women and 5 men (0.29%) had bladder cancer. Of the 850 chronically catheterized patients the incidence was 0.7%. One patient with cancer performed intermittent catheterization for a rate of 0.23% in this group. In a subgroup of 70 patients treated with cyclophosphamide 5 chronically catheterized patients (5.7%) had bladder cancer. Hematuria was the most common presenting symptom. These data were compared with those in the literature on bladder cancer in spinal cord injury. CONCLUSIONS: These data suggest a possible synergistic role of cyclophosphamide and chronic catheterization in the induction of secondary bladder cancer. Regular cystoscopy is warranted in these patients to allow early detection of bladder tumors. Nitric oxide metabolism may be an important factor in the carcinogenesis of this type of bladder cancer.     

Epilepsy in patients with multiple sclerosis: radiological-clinical correlations

This study was performed to determine whether the stimulatory effect of plasma angiotensin II (ANG II) on arginine vasopressin (AVP) and oxytocin (OT) secretion in humans is mediated by AT1 subtype receptors. For this purpose, the effects of the AT1 receptor antagonist losartan (50 mg orally) or a placebo on the AVP and OT responses to ANG II (intravenous infusion for 60 minutes of successively increasing doses of 4, 8, and 16 ng/kg min; each dose for 20 minutes) administration were evaluated in seven normal men. In additional experiments, the same subjects were tested with losartan (50 mg orally) alone or placebo alone. Neither losartan nor placebo given alone modified the basal levels of AVP and OT. ANG II infusion induced significant increments in both serum AVP and OT levels (mean peaks were 1.55 and 1.41 times higher than baseline, respectively). Both hormonal responses to ANG II were completely abolished by pretreatment with losartan. These data provide evidence of AT1 receptor involvement in mediation of the ANG II-stimulating effect on AVP and OT secretion.     

Influenza virus vaccination of patients with multiple sclerosis

Our previous data showed that at least five PKC isoforms (alpha, delta, zeta, lambda and tau) were present in the decidualization. In this study, we then localized the PKC alpha and zeta by immunohistochemistry in the decidualized uterine tissues. The decidualized uterine tissues were induced by trauma-stimulation and fixed in formalin. The immunofluorescence were photographed by confocal microscope. The data revealed that the fluorescence of PKC alpha was present in the deciduomata and myometrium. In the deciduomata, PKC alpha was mainly located in the surrounding nuclear. This phenomenon of localization was especially performed on day 2 and 3 of the decidualization, just on the time of higher frequence of cell mitosis. Since the myometrium with hypertrophy did not display the phenomenon of perinuclear localization, these suggested that the expression and localization of PKC alpha may be associated with the cell proliferation. On the other hand, the PKC zeta was also present and distributed broadly in the deciduomata and myometrium. This expression was increased and similar to the previous Western blot studies. Thus, the data confirmed that the various expression and localization of PKC isoforms may be correlated with the development of deciduomata.     

The metabolic characteristics of patients with multiple sclerosis

A comprehensive clinical and biochemical evaluation has been carried out in patients with multiple sclerosis (MS). Measured in the patients' blood were levels of cholesterol, triglycerides, malonic dialdehyde, and superoxidedysmutase activity. The interrelationship revealed between the above measures provides a deeper insight into the mechanisms of pathometabolism in MS.     

Identification of glial cell proliferation in early multiple sclerosis lesions

Multiple sclerosis (MS) is a chronic inflammatory disease of the central nervous system which leads to destruction of myelin sheaths. The patterns of cell proliferation in the early course of the disease are largely unknown. The present study used immunohistochemical identification of proliferating glial cells in stereotactic brain biopsy material of eight patients with early chronic MS. Double-labelling with the proliferation marker MIB-1 detected proliferating oligodendrocytes (MOG), astrocytes (GFAP) and microglia/macrophages (Ki-M1P). The majority of proliferating cells were macrophages/microglia when compared with oligodendrocytes (P > 0.005) or astrocytes (P > 0.0005); only a minor proportion of microglia/macrophages, however, proliferated in situ. Astrocytic and oligodendroglial proliferation was sparse to absent and showed significant variations between different patients. There were statistically significant differences when comparing the amount of proliferation between lesions of different demyelinating activity: highest numbers of proliferating cells were found in early active lesions compared with demyelinated and early remyelinated lesions (P > 0.05) or the periplaque white matter (P > 0.01). MOG-positive oligodendrocytes proliferated occasionally in the early stages of lesion formation; this proliferation occurred in four cases but was independent of the stage of the disease. Since MOG is expressed by mature oligodendrocytes, and not by immature precursors, this might suggest a potential role for the proliferation of mature surviving oligodendrocytes with subsequent remyelination.     

Endothelial cell integrin laminin receptor expression in multiple sclerosis lesions

A model that explains natal dispersal in resident screech-owls is presented and examined. The model is based on interactions among hormonal changes, body condition and social stimuli. It predicts that corticosterone, an adrenal glucocorticoid known to stimulate locomotor and foraging activity, increases in blood plasma prior to dispersal through a combination of endogenous and exogenous events. This mediates the locomotor activity that underlies dispersal behaviour. Juveniles in good body condition (i.e. those with sufficient fat reserves) will disperse when corticosterone increases. Birds in poor body condition will not, but they will increase their foraging activity under the influence of corticosterone. Dispersal of siblings will reduce aggression and/or competition for food, enabling the remaining juveniles to improve their body condition and disperse. Initial studies on screech-owls, Otus asio and O. kennicottii, have produced results that are generally consistent with the model. For example, captive juvenile screech-owls showed increased locomotor activity in the weeks leading up to the time when free-living juveniles are dispersing, and activity levels declined thereafter. Peaks in corticosterone corresponded with periods of high locomotor activity (i.e. at the time of dispersal) in captive owls. Finally, field studies indicate that dominant juveniles, which are presumably in better physical condition, initiated dispersal before their more subordinate siblings. Copyright 1998 The Association for the Study of Animal Behaviour.     

Magnetization transfer ratios of multiple sclerosis lesions with variable durations of enhancement

Papillary fibroelastomas are rare endocardial growths that most commonly occur on the cardiac valves. Whether papillary fibroelastomas represent true neoplasms, hamartomas, or degenerative changes is debatable. Whatever their origin, papillary fibroelastomas have a characteristic gross and microscopic appearance, are usually solitary, and are almost always incidental findings at autopsy or during cardiac surgery. We report a case of sudden death caused by occlusion of the right coronary artery ostium by a papillary fibroelastoma of the aortic valve. We discuss the gross and microscopic features, differential diagnosis, and etiology and pathogenesis of this rare and interesting cardiac lesion.     

Pressor response to isometric exercise in patients with multiple sclerosis

The purpose of this study was to determine whether patients with multiple sclerosis (MS) would show attenuated heart rate and/or pressor responses to isometric handgrip exercise. Patients with MS (30 males, 74 females, aged 23-61 yr) and control subjects (9 males, 16 females, aged 25-47 yr) performed isometric handgrip exercise at 30% of maximal voluntary contraction (MVC) to fatigue. Systolic, diastolic, and mean arterial pressure (MAP) increased linearly in both groups, but were significantly lower (P < 0.05) in patients with MS at 20%, 40%, 60%, 80%, and 100% of exercise duration. Mean change in MAP at fatigue was +47.9 mm Hg for controls and +28.2 mm Hg for patients with MS, with 18 patients with MS between -6 mm Hg and +15 mm Hg. Heart rate increased normally in patients with MS. To predict change in MAP at fatigue in patients with MS, stepwise regression analysis using six variables yielded an R2 of 0.26. These data suggest that in some patients MS lesions exist in areas of autonomic cardiovascular control that result in attenuated pressor responses to exercise. In 17% of patients tested, attenuation was profound. Data also suggest an abnormal dissociation between the heart rate and pressor response to static work in patients with MS.     

Clinical characterization of patients with multiple sclerosis defined in Cuba

INTRODUCTION: Since 1975 no studies have been done in Cuba defining the clinical characteristics of patients with multiple sclerosis (MS). OBJECTIVE: To describe the characteristics of a group of Cuban patients with definite clinical MS. MATERIAL AND METHODS: Fifty eight patients with definite clinical MS were studied (Poser et al) with normal motor (VCM) and sensory (VCS) conduction velocities. Tests were done on them: clinical scale (Scripps), incapacity (EDSS) and quality of life (Steps), together with various complementary tests. Each patient was classified according to the way in which the disease evolved. Also the two commonest clinical types were compared and we applied the difference test between percentages of non-paired samples with an alfa level of 0.05. RESULTS: Onset of the illness in most cases was before the age of 40 (86.1%), 75.9% were women and 82.8% were white. In 15.3% there was a family history of MS. In 25.9% there were psychiatric disorders and trigger factors (43.1%. The most frequent initial symptoms were pyramidal (48.3%) sensorial (41.4%) and cerebellar (39.7%). Scripps scale scores were < 80 in 60.2%, in EDSS < 5 (61.9%) and in the Clinical Steps < 3 in 65.4%). Motor potentials (81.9%) somatosensory potential (PESS) (72.3%) and magnetic resonance imaging (MR) (76.4%) were the most abnormal results. Exacerbation-remission (ER) was the most frequent type of evolution (53.4%) generally affecting patients aged under 40 years old (p = 0.02), EDSS < 5 (64.4%), Scripps > 80 (61.2%), Steps < 3 (95.6%), pyramidal system involvement (58.5%), cerebellar (29.2%) and MRI abnormality (80%). The progressive primary form (PP) was the second most frequent (29.3%); 29.4% were under 40 years of age, had more marked changes in all functional system (100%), degree of incapacity and quality of life (100%). PESS (92.5%); the urodynamic tests 58.85%) were less positive on MRI (54.5%) as compared with the ER form. CONCLUSIONS: The differences found between the clinical forms ER and II indicate that there is greater deterioration in the PP form, probably due to age and more cerebellar and spinal cord involvement.     

Diagnostic studies of cerebrospinal fluid in patients with multiple sclerosis

The diagnostic criteria postulated by Poser necessitate clinical and laboratory CSF analysis for establishment of the diagnosis of definitive multiple sclerosis. The present paper reports methods for CSF examinations relating to multiple sclerosis with regard to the examinations suggested by the Charcot Foundation. In the course of CSF analysis, it is important to discriminate between the immunoglobulins present in normal amounts, those synthesized locally in pathological quantities and those penetrating across the damaged blood-CSF barrier. Normally, a parallel assay of CSF and serum specimens is carried out in the course of quantitative and qualitative protein analysis. In 37 patients with clinical multiple sclerosis, we determined the albumin and the immunoglobulin classes IgG, IgA and IgM, using laser nephelometry. An elevated IgG index was found in 76% of the cases, which points to local IgG snythesis and might be proof of the humoral immune response. The albumin quotient, which is suitable for examination of the integrity of the blood-CSF barrier, was within the reference range. Qualitative protein analysis was performed by means of electrophoresis on agarose-gel and isoelectric focusing. Agarose-gel electrophoresis revealed oligoclonal gammopathy in 68%, in contrast with the 91% demonstrated by isoelectric focusing. Comparison of the two kids of qualitative protein analyses indicated that isoelectric focusing was more sensitive for the detection of oligoclonal bands, in support of the literature finding.     

Magnetization transfer changes in the normal appearing white matter precede the appearance of enhancing lesions in patients with multiple sclerosis

Serial monthly magnetization transfer (MT) imaging was performed to evaluate whether a change of the normal appearing white matter (NAWM), which precedes the appearance of enhancing lesions, is seen in patients with multiple sclerosis (MS). Every 4 weeks for 3 months, 10 patients with relapsing-remitting MS were scanned with a T1-weighted sequence, 20 minutes after injection with 0.3 mmol/kg gadolinium-DTPA (Gd-DTPA). During each of the monthly sessions, MT and dual echo scans were also performed before Gd-DTPA injection. On coregistered images, the MT ratio (MTR) was measured in NAWM subsequently involved by enhancing lesions, in NAWM areas on the same slices but outside any present or future MR abnormality, and in enhancing lesions at the time of their appearance. Forty-eight new enhancing lesions with no corresponding abnormalities on previous scans were identified. Their average MTR was 33.1% (+/-8.4%). Three, 2, and 1 month before enhancement appearance, the mean MTR in NAWM, measured from areas corresponding to future enhancing lesions, was significantly lower than the mean MTR in NAWM outside enhancing areas; the MTR decreased steadily as the time when the enhanced lesion approached. These results suggest that changes in the NAWM of patients with MS occur before lesions become evident on conventional MRI scans.     

Physical and occupational therapy in the treatment of patients with multiple sclerosis

The interdisciplinary approach to the management of MS patients includes the services of both physical and occupational therapy. These professions complement one another in their concerted effort to mobilize the patient, thereby minimizing the symptoms of progressive weakness, fatigue, and spasticity. The ambulant patient is far less likely to develop complications of inactivity such as contractures, decubitus ulcers, venous thrombosis, or osteoporosis (with its associated fatigue fractures), as well as bowel or bladder complications.     

Comprehensive rehabilitation of multiple sclerosis patients

Rehabilitation of Multiple Sclerosis patients is one of the most specific problems because of its variable and unforeseeable course. Rehabilitation procedures of those patients must be performed individually and very elastic in every case. In this elaboration the most commonly appeared forms and course of MS have been presented. According to it the planing of the rehabilitation has been adapted. Basic rules of the exercises during the relapse and during the remission have been presented. The greatest attention has been paid to the problems of managing spasticity and the reeducation of neurogenic bladder.